because the C-type genes are deleted in both lines, and the resulting neuronal cell loss dominates the phenotypes. In the absence of apoptosis, however, the neonatal lethality in C-type isoform knockouts is rescued since neural circuitries essential for postnatal survival are largely preserved by the remaining 19 A-type and B-type Pcdhgs. By contrast, Pcdhgdel/del;Bax−/− compound mutants still die at P0 since the entire Pcdhg cluster is deleted, which severely compromises critical wiring and synaptic function carried out by all isoforms synergistically. The dual role of Pcdhg cluster in neuronal survival and neuronal wiring is thus elegantly accomplished by functional and regulatory diversification of its isoforms.
